Humans and animals with certain conditions are either not able to or preferably do not take nutrition by conventional means. Such individuals can have sustenance administered parenterally such as by the use of a venous drip or enterally in the form of a specific liquid formulation delivered via intubation of the gastrointestinal tract. There are obvious disadvantages to administering sustenance parenterally in so far as the risk of trauma and infection is greatly increased and the rate at which material that can be administered is quite low. Moreover, certain types of material cannot be administered, for example, dietary fibre. Additionally there are risks in having a gastrointestinal system which is inactive for any extended length of time due to the absence of fibre and other poorly digestible materials as it can lead to atrophy and to a range of other histo-pathological changes to various regions and even in the shorter term diminishes the well being of an individual.
Food formulations for clinical conditions may be administered orally and that is the preferred route as it is the normal means of food ingestion. However, for certain specific conditions it is necessary or at least advantageous to administer the formulation enterally by a tube feeding systems such as by a nasogastric tube which delivers nutrients directly to the stomach.
The requirement for enteral feeding might be relatively short term for example where a patient or other individual is treated for a clinical condition where the patient may be unable to masticate, swallow or retain conventional forms of food. Alternatively the patient might be suffering from a condition that requires longer term treatment and enteral feeding might be administered at the residence of the patient for a prolonged period.
Enteral formulations, especially those, used for short periods are intended to replace the normal diet and so contain materials that reflect such diets, and these include nitrogenous material such as proteins, protein hydrolysates, peptides or amino acids, carbohydrates (whole or partially hydrolysed), lipids, vitamins and essential minerals are thus generally delivered as emulsions. No particular attention is given to maintaining an active colon for short term administration. It is recognised that an inactive large bowel in the longer term is undesirable, and commercial formulations which have “added fibre” are available, with a view of maintaining such activity. These formulations generally include a fermentable resistant starch or a fermentable non-starch carbohydrate that is resistant to digestion by human enzymes in the small bowel but is fermentable by the microflora in the large bowel. Cope et al. in U.S. Pat. No. 5,403,826 refer to the inclusion of dietary fibre to enteral formulations and exemplify the use of soy polysaccharides. These polysaccharides are in large part digested in the ileocaecal region and the proximal large bowel with none or only small amounts reaching the distal bowel (Annison. G. & Topping, D. L. (1994) Resistant starch: Chemical structure vs physiological function. Ann. Rev. Nutr. 14: 297–320) and the levels used in the formulation are quite low. Garleb et al. in U.S. Pat. No. 5,444,054 refers to the inclusion of dietary fibres and indigestible oligosaccharides so that SCFAs may be formed in the large bowel. Reference is also made to Green et al in U.S. Pat. No. 5,792,754 where a mixture of resistant fibre is provided which is claimed to provide for deliver a balance of activity alone the length of the gastrointestinal tract. The inventors believe that Cope, Garleb and Green, as well as commercially available formulations all suffer from the inability to deliver sufficient fibre to give an adequate elevation of short chain fatty acid (SCFA) levels in the colon.
Whilst the “fibre added” enteral formulations do go some way to alleviating the problems of a totally inactive gastrointestinal tract the degree of fermentation in the large bowel is simply not enough, particularly for patients that are fed enterally for extended periods. The relatively low level of delivery of fermentable fibre to the colon would be exacerbated where the medical treatment received by the patient has a marked impact on the microflora of the patient which therefore cannot or is inefficient at transforming fibre to SCFAs.
A consequence of long term enteral feeding is the manifestation of certain disorders of the caecum and colon due to at least in part inactivity and lack of nutrient. Such disorders might include atrophy and perforation of the bowel, the overgrowth of the normal microflora of the bowel by organisms which might potentially be pathogens and diarrhoea.
One primary restriction on the capacity to deliver is the quantity of fibre that can physically be delivered through a feeding tube such as a nasogastric tube rather than a reluctance to increase levels in enteric formulations. Nasogastric tubes are rather difficult to put into place and are unpleasant for the patient and thus the outside diameter of the tube is kept as small as possible with a consequent small internal diameter. Not only is the internal diameter a consideration but a pump or gravity is generally used to move the formulation through the tube. This means that the liquid within the tube is also under compression, so that any viscosity of the fluid is further compounded. The intrinsic viscosity of soluble fibre and protein in the partially or fully hydrolysed state can be high and thus poses a limitation. Some of the components of these formulation may be delivered as insoluble suspensions, however, the provision of insoluble suspensions is particularly undesirable for nasogastric application, because of the difficulties associated with sedimentation and phase separation and the difficulty of resorting to increased viscosities to alleviate settling out. The very much preferred approach to nasogastric application is to provide the solids in soluble form, which are supplied together with the fat component to form an emulsion.
A suggestion has been made in U.S. Pat. No. 5,919,822 by Cotter et al. in light of the restricted capacity of enteral formulation to include fibre provide SCFAs in enteral and parenteral formulations. Cotter et al do however not provide any data in terms of the efficacy of the delivery of SCFA, and it is believed that the predominance of the SCFA will be degraded before reaching the large bowel so that the formulation provides little benefit especially to the distal colon. The direct delivery of SCFA has only be achieved by an enema (Sheppach et al. (1992) Gastroenterology: 10: 51–56), or when complexed with a carrier (WO 95/13801).
It is believed by the inventors that the enteral formulations suggested to date do not supply an adequate amount of short chain fatty acids to the large bowel or at least do so inefficiently. Additionally in the event of a highly altered microflora of the large bowel which might result from chemotherapy or antibiotic treatment, the often quite complex transformation that are required to produce beneficial short chain fatty acids cannot be performed efficiently. Furthermore providing an enteral formulation that delivers benefit, in the form of elevated amounts of short chain fatty acids to the large bowel in a short time span has to the knowledge of the inventors not been done before.
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